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SERT is the target for many antidepressant medications as well as psychostimulants such as cocaine and ecstasy (3,4-methylenedioxymethamphetamine). SERT belongs to the SLC6 family of ion-coupled transporters and is structurally related to several other transporter families. SERT was studied in the 1970s and 1980s using membrane vesicles isolated from blood platelets. These studies led to a proposed stoichiometry of transport that has been challenged by high-resolution structures of SERT and its homologues and by studies of SERT electrophysiology. Here, we review the original evidence alongside more recent structural and electrophysiological evidence. A self-consistent picture emerges with surprising insights into the ion fluxes that accompany 5-HT transport.<\/jats:p>","DOI":"10.1085\/jgp.201812066","type":"journal-article","created":{"date-parts":[[2019,9,30]],"date-time":"2019-09-30T14:56:45Z","timestamp":1569855405000},"page":"1248-1264","update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":86,"title":["Serotonin transport in the 21st century"],"prefix":"10.1085","volume":"151","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7622-4110","authenticated-orcid":true,"given":"Gary","family":"Rudnick","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Yale University School of Medicine, New Haven, CT 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3637-260X","authenticated-orcid":true,"given":"Walter","family":"Sandtner","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2019,9,30]]},"reference":[{"key":"2023072705301087700_bib1","doi-asserted-by":"publisher","first-page":"3268","DOI":"10.1016\/S0006-3495(02)75328-9","article-title":"Flux coupling in the human serotonin transporter","volume":"83","author":"Adams","year":"2002","journal-title":"Biophys. 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